Polysulfides are possible H2S‐derived signaling molecules in rat brain

Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org